Two agents are currently approved for the treatment of chronic hepatitis B: interferon alfa and lamivudine. Each agent has inherent limitations for use in the treatment of chronic hepatitis B. Interferon alfa is effective in a small number of patients and has serious side effects that limit its tolerability. The efficacy of lamivudine is limited by the emergence of drug-resistant hepatitis B virus (HBV) mutants, restricting its utility as a long-term therapy for chronic hepatitis B. As a result, a large proportion of chronic hepatitis B patients continue to be in need of a safe and efficacious therapy. This article provides an integrated analysis of the safety and efficacy of a new nucleotide analogue, adefovir dipivoxil, based on emerging data from recent studies. The study groups include patients with hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic hepatitis B; lamivudine-resistant patients with compensated liver disease; lamivudine-resistant patients coinfected with the human immunodeficiency virus (HIV); and lamivudine-resistant pretransplant and posttransplant patients with decompensated liver disease. Adefovir dipivoxil 10 mg/d demonstrated potent anti-HBV activity consistently across this broad range of patient populations and was well-tolerated. Adefovir dipivoxil's effects include rapid and sustained virological, serological, histological, and biochemical responses, with minimal adverse effects. Significant histological improvement was seen in all patient subgroups at 48 weeks.